Substance P raises neuronal membrane excitability by reducing inward rectification

Abstract

Much interest has recently centred on the properties of peptides that modulate the excitability of nerve cells. Such compounds include the undecapeptide substance P, which is particularly well established as an excitatory neurotransmitter, and we examine here its effects on magnocellular cholinergic neurones taken from the medial and ventral aspects of the globus pallidus of newborn rats and grown in dissociated culture. These neurones have previously been shown to respond to substance P3 and are analogous to the nucleus basalis of Meynert in man, which gives a diffuse projection to the cerebral cortex and whose degeneration is the likely cause of Alzheimer's disease. Substance P depolarizes these cultured neurones by reducing an inwardly rectifying potassium conductances; this conductance has been found in several neuronal types and has similar properties to those of certain other cells. As discussed below, modulation of inward (or anomalous) rectification by substance P implies a self-reinforcing element to the depolarization caused by the peptide.

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

“…Thus, functions of the ganglia were analyzed by examining the production of NADPH diaphorase and substance P in the neuronal cells. NADPH diaphorase is identical to nitric oxide synthase (26)(27)(28)(29) and nitric oxide functions as an inhibitory neurotransmitter to relax smooth muscle (30), while substance P is an excitatory neurotransmitter to contract circular smooth muscles (31,32). NADPH diaphorase positive neuronal cells were dense in the proximal colon of Ncx Ϫ / Ϫ mice with (data not shown) or without megacolon (Fig.…”

Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: comparison of IRK2 with IRK1 and IRK3

“…current in cholinergic neurons of basal nucleus, which raises excitability of the neurons [13][14][15]. Because both intracellular ATP and phosphorylation were reported to be essential to maintain IRK1 channel activity [16], IRKs can be targets of protein kinases and phosphatases.…”

Phosphorylation‐independent inhibition by intracellular cyclic nucleotides of brain inwardly rectifying K+ current expressed in Xenopus oocytes

“…Inhibition of K + currents results in an increase of neuronal cellular excitability by decreasing resting membrane potential, increasing the action potential duration and reducing afterhyperpolarization. It has been reported that substance P and thyrotropin-releasing hormone inhibit neuronal inwardly rectifying K + current [19][20][21]. This inhibition is not voltage-dependent, and involves PTX-insensitive G proteins and protein kinase C activation in their signalling.…”